1. In an attempt to determine the mechanism whereby enzymes are removed from the circulating plasma, purified rabbit-muscle lactate dehydrogenase-5 was labelled with 125I and injected intravenously into rabbits. During the first hour after injection enzyme activity and radioactivity disappeared from the plasma at comparable fast rates, which are attributed mainly to distribution of the enzyme throughout the extracellular fluid. This was followed by a phase lasting about 7 h during which enzyme activity disappeared at a faster rate than the radioactivity, an observation indicating either intravascular breakdown of the enzyme protein or its degradation in the tissues, followed by release of labelled fragments into the circulation. Enzyme activity then reached a constant value and the plasma radioactivity continued to decrease at a slower exponential rate; it is suggested that this is due to removal of breakdown products.
2. The radioactivity of the tissues was measured at various time-intervals after injection. After 2 h and 8 h highest concentrations were found in the spleen, liver, jejunum and duodenum. Relatively high concentrations were also found in the intestinal juices throughout the period of study, an observation which suggests that discharge via the small intestine is a major route whereby inactivated enzyme fragments are removed from the circulation.
3. About 5% of the injected radioactivity was recovered in the faeces during the first 3 days, and the urine accounted for 73% during the same period. About 35% of the urinary radioactivity was shown by silver nitrate precipitation and by chromatography to consist of free iodide and the remainder appeared to consist of radio-iodinated amino acids or peptides. Free mono- and di-iodotyrosine were identified among the products. These results suggest that further breakdown in the intestine is followed by absorption of the products, which are excreted in the urine.